Seldes was born in Manhattan, the daughter of Alice Wadhams Hall, a socialite, and Gilbert Seldes, a journalist, author, and editor. Her uncle was journalist George Seldes. She had one brother, Timothy. Seldes's paternal grandparents were Russian Jewish immigrants, and her mother was from a "prominent WASP family," the "Episcopalianblue-blooded Halls." She grew up in a creative environment, studying acting at the Neighborhood Playhouse. Her maternal aunt, Marian Wells Hall (died 1972), was a prominent interior decorator.
Trained for the stage, Seldes made her Broadway theatre debut in 1948 in a production of Medea. She went on to an illustrious career in which she earned five Tony Award nominations, winning her first time out in 1967 for A Delicate Balance. In addition to performing in live theatre, Seldes began acting in television in 1952 in a Hallmark Hall of Fame production that marked the first of many guest star roles. She also performed in a number of motion pictures and in radio plays. In the mid-1960s, Seldes recorded five albums for Folkways Records of famous works of literature, including two recordings of poetry by Robinson Jeffers. Between 1974 and 1982, she appeared in 179 episodes of the CBS Radio Mystery Theater. In 1992, she appeared in an episode of Murphy Brown as the title character’s eccentric Aunt Brooke.
In December 2008, for their annual birthday celebration to "The Master", Noël Coward, the Noël Coward Society invited Seldes as the guest celebrity to lay flowers in front of Coward's statue at New York's Gershwin Theatre, thereby commemorating the playwright’s 109th birthday. Seldes was the recipient of a 2010 Tony Lifetime Achievement Award. "All I've done is live my life in the theater and loved it ... If you can get an award for being happy, that's what I've got."
Seldes had one child, Katharine, by her first marriage to Julian Claman. They were divorced in 1961. Seldes stated that the marriage to Claman was violent. "If I sound a little vague about that marriage, it's because I don't understand the person in it. Me. I literally didn't know that people could be abusive." Seldes left the marriage after her father noticed marks on her face. Seldes was married to screenwriter/playwrightGarson Kanin from 1990 until his death in 1999.
Seldes died on October 6, 2014, in her Central Park South apartment, aged 86 years. She was survived by her daughter, brother, sister-in-law, and extended family.
The cause of her death was not released. However, in 2017, it was reported that a documentary about her life, Marian, by director R.E. "Rick" Rodgers, chronicling Seldes' last years, had created "consternation in the theater world" as a "horrific, intrusive depicting of her slide into dementia".
Gunsmoke: Played Mrs. Cullen in "Indian White" (1956)
Have Gun – Will Travel: Played Christie Smith in "The Bride" (1957), and Mollie Stanton in "The Teacher" (1958)
Perry Mason: Played Mary K. Davis in "The Case of the Screaming Woman" (1958)
The Court of Last Resort: Played Roberta Farrell in "The Frank Clark Case" (1958), and Mary Morales in "The Mary Morales Case" (1958)
Half Hour to Kill: Played Joyce Field. Half Hour to Kill was a proposed but unrealized television series mystery show with episodes hosted by Vincent Price and planned to occasionally star him as well. Released to the home movie market as Freedom to Get Lost, with Price playing scientist Gene Wolcott and Seldes playing an undercover security agent tracking him. The episode is available on the DVD titled Vincent Price – The Sinister Image. (1958)